Brain TSPO imaging and gray matter volume in schizophrenia patients and in people at ultra high risk of psychosis: An [11C]PBR28 study

Abstract

Patients with schizophrenia show whole brain and cortical gray matter (GM) volume reductions which are progressive early in their illness. Microglia, the resident immune cells in the CNS, phagocytose neurons and synapses. Some post mortem and in vivo studies in schizophrenia show evidence for elevated microglial activation compared to matched controls. However, it is currently unclear how these results relate to changes in cortical structure.

Methods: Fourteen patients with schizophrenia and 14 ultra high risk for psychosis (UHR) subjects alongside two groups of age and genotype matched healthy controls received [¹¹C]PBR28 PET scans to index TSPO expression, a marker of microglial activation and a 3T MRI scan. We investigated the relationship between the volume changes of cortical regions and microglial activation in cortical GM (as indexed by [¹¹C]PBR28 distribution volume ratio (DVR).

Results: The total cortical GM volume was significantly lower in SCZ than the controls [mean (SD)/cm³: SCZ=448.83 (39.2) and controls=499.6 (59.2) (p=0.02) but not in UHR (mean (SD)=503.06 (57.9) and controls=524.46 (45.3) p=0.3). Regression model fitted the total cortical GM DVR values with the cortical regional volumes in SCZ (r=0.81; p<0.001) and in UHR (r=0.63; p=0.02). We found a significant negative correlation between the TSPO signal and total cortical GM volume in SCZ with the highest absolute correlation coefficient in the right superior-parietal cortex (r=-0.72; p=0.006).

Conclusions: These findings suggest that microglial activity is related to the altered cortical volume seen in schizophrenia. Longitudinal investigations are required to determine whether microglial activation leads to cortical gray matter loss.

Keywords: Brain volume; Gray matter; Microglia; PET; Psychosis; Schizophrenia.